This invention relates to compositions for forming a radioactive material suitable for use in the body of a subject. More particularly, it concerns a radioactive material, such as a polymer or a metal, that can be used for example, as a suture material, or as an implantable device, such as vaso-occlusive coil. In addition, the radioactive compositions can be also begin conjunction with other additives to form a biologically active anatomical occlusion within the vasculature of a patient. The radioactivity material allows for visualization in situ and can be also be used to affect cell growth in the surrounding areas.
This invention relates to radio-isotope containing material, for example a radioactive polymer or metal. The resulting radioactive materials may be used as visible sutures or can be used in conjunction with liquid-based vaso-occlusive compositions or with mechanical implantable devices, such as vaso-occlusive coils. The radioactive materials may be visualized and may be chosen such that they affect (e.g., promote or inhibit) growth of cells in and around the site of use.
The addition of radioactive isotopes to implantable stents has been described. (See, e.g., Carter A J (1998) Int. J Radiat. Oncol. Biol. Phys. 41(1):127-33 and Hehrlein et al. (1997) Semin Inter Cardio 2:109-113). These radioactive stents have been shown to inhibit both restenosis and the formation of smooth muscle. Typically, the radioactive isotope is impregnated into the stent (Janicki et al. (1997) 24:437-445), electrodeposited onto the stent (Hafeli et al. (1998) Biomaterials 19:925-933) or ion beam deposited on the stent (Fehsenfeld et al. (1998) Semin Interv Cardiol. 3:157-161).
The use of bioabsorable compositions for medicinal purposes has been described. U.S. Pat. No. 5,747,637 describes suture materials made of polyesters such as polylactic acid, polyglycolic acid and a lactic acid-glycolic acid copolymer. The suture material is bioabsorbable via a nonenzymatic hydrolyzation process in a living body. The decomposition products such as lactic acid and glycolic acid are finally converted through a metabolic pathway to carbon dioxide and water, and externally discharged.
Commonly-owned co-pending application U.S. Ser. No. 09/351,769 describes occlusive agents which may be made from a precursor composition containing at least one biodegradable, polymeric precursor component and at least one biologically active agent which encourages cellular attachment. The polymeric precursor component can be precipitated to form a solid occlusion mass in an anatomical cavity. Unlike known precipitating polymers, these bioreactive occlusive agents contain bioactive materials and are typically dissolved in biologically tolerated solvents.
Polymeric materials have also been used in conjunction with implantable devices such as stents, catheters and vaso-occlusive devices. Examples of such vaso-occlusive devices are helically wound coils, ribbons and braids. Various shaped coils have been described. For example, U.S. Pat. No. 5,624,461 to Mariant describes a three-dimensional in-filling vaso-occlusive coil. U.S. Pat. No. 5,639,277 to Mariant et al. describe embolic coils having twisted helical shapes and U.S. Pat. No. 5,649,949 to Wallace et al. describes variable cross-section conical vaso-occlusive coils. A random shape is described, as well. U.S. Pat. No. 5,648,082 to Sung et al., describes methods for treating arrhythmia using coils which assume random configurations upon deployment from a catheter. U.S. Pat. No. 5,537,338 describes a multi-element intravascular occlusion device in which shaped coils may be employed. U.S. Pat. No. 5,826,587 entitled xe2x80x9cUltrasoft Embolization Coils with Fluid-Like Propertiesxe2x80x9d by Berenstein et al., describes a coil having little or no shape after introduction into the vascular space.
There are a variety of ways of discharging shaped coils and linear coils into the human vasculature. In addition to those patents which apparently describe only the physical pushing of a coil out into the vasculature (e.g., Ritchart et al.), there are a number of other ways to release the coil at a specifically chosen time and site. U.S. Pat. No. 5,354,295 and its parent, U.S. Pat. No. 5,122,136, both to Guglielmi et al., describe an electrolytically detachable embolic device. Mechanically detachable devices are also known, as in for instance, U.S. Pat. No. 5,234,437, to Sepetka; U.S. Pat. No. 5,250,071, to Palermo; U.S. Pat. No. 5,261,916, to Engelson, and U.S. Pat. No. 5,304,195, to Twyford et al.
Vaso-occlusive coils have also been treated with variety of substances. For instance, U.S. Pat. No. 4,994,069, to Ritchart et al., describes a vaso-occlusive coil that assumes a linear helical configuration when stretched and a folded, convoluted configuration when relaxed. The stretched condition is used in placing the coil at the desired site (by its passage through the catheter) and the coil assumes a relaxed configurationxe2x80x94which is better suited to occlude the vesselxe2x80x94once the device is so placed. Ritchart et al. describes a variety of shapes. The secondary shapes of the disclosed coils include xe2x80x9cflowerxe2x80x9d shapes and double vortices. The coils may be coated with agarose, collagen, or sugar. Radio-opaque coatings, typically metallic in nature, have also been applied to such devices.
U.S. Pat. No. 5,669,931 to Kupiecki discloses coils that may be filed or coated with thrombotic or medicinal material. U.S. Pat. No. 5,749,894 to Engleson discloses an aneurysm closure method which involves a reformable polymer.
U.S. Pat. No. 5,536,274 to Neuss shows a spiral implant which may assume a variety of secondary shapes. Some complex shapes can be formed by interconnecting two or more of the spiral-shaped implants. To promote blood coagulation, the implants may be coated with metal particles, silicone, PTFE, rubber latexes, or polymers.
None of these documents disclose compositions comprising a polymer and at least one radioactive material suitable for use in medicinal purposes. Further, none describe vaso-occlusive devices used in conjunction with these compositions or vaso-occlusive devices which are themselves made to be radioactive or to contain radioactive materials.
Thus, this invention includes radioactive materials which can be used to create material (e.g., sutures, liquid-based vaso-occlusive material or solid vaso-occlusive devices) for use in situ. The materials for use in situ generally contain sufficient amounts of radioactivity such that compositions are fluoroscopically visible in situ, have an effect on surrounding cells (e.g., is bioactive) or are both visualizable and bioactive.
In one aspect the invention includes a composition comprising a polymeric component and at least one radioactive material. In certain embodiments, the radioactive material is dispersed throughout the polymeric component. In other embodiments, the radioactive material is deposited onto the surface of the polymeric component. In yet other embodiments, the composition further comprises a biologically active material. The polymeric component may be biodegradable (e.g., a biodegradable polyester such as polyglycolic acids, polylactic acids, and their copolymers) and/or bioactive. The radioactive material may be fluoroscopically visible in situ.
In another aspect, the invention includes a composition for occluding an anatomical cavity comprising
(a) a polymeric occlusion-forming component and
(b) a radioactive material, wherein said polymer precipitates when introduced into the anatomical cavity. In certain embodiments, the polymeric occlusion-forming component comprises a biodegradable component reactively forming a polymer mass when introduced into the anatomical cavity.
In another aspect, the invention includes a vaso-occlusive device comprising a polymeric component and at least one radioactive material. The vaso-occlusive device may comprise a mechanical vaso-occlusive device, for example a coil. The radioactive polymeric composition can be braided, wound, coated or otherwise associated with the device (e.g., coil). In certain embodiments, the device (e.g., coil) is radioactive.
In yet another aspect, the invention includes a vaso-occlusive device comprising a radioactive polymer, radioactive metal or mixture thereof. In certain embodiments, a mechanical vaso-occlusive device, for example a coil, is also included.
In a still further aspect, the invention includes a solid occlusive mass comprising a radioactive material and a biodegradable polymer, for example a polyester such as polygylcolic acids, polylactic acids and their copolymers. The occlusive mass may include at least one bioactive material, for example, collagen, fibrinogen, vitronectin, plasma proteins, growth factors, synthetic peptides of these and other proteins having attached RGD (arginine-glycin""e-aspartic acid) residues at one or both termini, cell adhesion peptides, oligonucleotides, full or partial DNA constructs, natural or synthetic phospholipids, polymers with phosphorylcholine functionality, and polynucleotide sequences encoding peptides (e.g., genes) involved in wound healing or promoting cellular attachment.
In another aspect the invention includes a kit for forming a composite biologically active anatomical occlusion in an anatomical cavity, comprising:
a) at least one solid vaso-occlusive device, and
b.) a liquid precursor composition comprising:
i. ) a biodegradable, polyester material and
ii.) a radioactive material, wherein said liquid precursor composition forms a radioactive occlusion mass when introduced into the anatomical cavity.
In certain embodiments, the liquid precursor composition further comprises a bioactive material and the at least one solid vaso-occlusive device comprises a coil. In further embodiments, the biodegradable polyesters may be polyglycolic acids, polylactic acids, polycaprolactone, and their copolymers and their copolymers with trimethylene carbonate, polyhydroxybutyrate and polyhydroxyvalerate and their copolymers or polyanhydride. The liquid precursor composition may further comprise a biologically tolerated solvent.
In a further aspect, the invention includes a procedure for at least partially filling an anatomical cavity comprising the steps of:
a.) introducing a polymeric occlusion-forming component and a radioactive material, wherein said polymer precipitates when introduced into the anatomical cavity into said anatomical vessel; and
b.) precipitating said biodegradable, polymeric occlusion-forming component and said biologically active component into said biologically active occlusion mass in said anatomical cavity.
The procedure may further comprise the step of introducing a mechanical vaso-occlusive device into said anatomical cavity, for example prior to introducing the radioactive polymeric occlusion-forming component.
These and other embodiments of the subject invention will readily occur to those of skill in the art in light of the disclosure herein.